Ultrasonically marked system for therapy delivery
Technical field This invention relates to cardiac therapy, particularly to the guiding apparatus for systems for gene therapy or other pharmaceutical therapy modes. More particularly, the invention pertains to the system for guiding procedures performed with direct application of medical agents directly into the heart muscle or other body structures.
Summary of the invention Control of intracorporeal administration of medical agents is solved by this invention. It enables controlled therapeutic or diagnostic punctures within the heart or other structures in the body that are normally accessible only with catheters or similar devices. The said medical agent may be stem cells, a gene agent, a chemotherapy agent or any type of injectable drug. In a case when implantation is required at a well-defined depth, our invention serves to strictly control this depth. In addition, the placement procedure is guided by ultrasound echography. The puncture is done in two steps. The first step is to bring the puncture set to the right place and in contact with the tissue to be punctured. The second step is the actual puncture with administration of a medical agent or aspiration of a diagnostic sample. Our device consists of a hollow introducer catheter that is the outer guiding means and within it (inside) another catheter with a puncture needle at its distal end. The inside member can be a flexible puncture needle. The introducer catheter is used to maneuver the tip of the device to the point of interest. The internal puncture catheter or flexible needle is than pushed out to perform a therapeutic or diagnostic puncture. Both, the exact positioning and exact puncture need guidance and control to make it essentially safer and more exact compared to an x-ray guided procedure. The method for positive ultrasonic localization of a point on an indwelled device, e.g. the said outer or the said inner needle catheter, consists of ultrasonic marking of the catheter and the use of a transponder to generate a visible mark on
the ultrasound scanner screen. Thus, the present method includes an imaging ultrasound scanner and the herewith-described set of ultrasonically marked puncture catheters. One or more miniature piezoelectric marker transducers are mounted at the tip of the outside (introducer) catheter and a separate transducer is mouhted onto the puncture (needled) catheter. The marker transducer electrodes are connected to the electrical conductors that connect it along the catheter to an outside electrical connector at the proximal end of the catheters. When the transducer on the catheter tip is in the scanning area, ultrasound pulses from the transducer of the echoscope energize it. Thus generated high frequency pulses are taken via built-in electrical conductors to the localization transponder. The transponder localization system is a pulse train generator triggered by signal from the said marker transducer when the marked part of the catheter is within the ultrasonic scanning plane or area. When an ultrasonic pulse reaches the marker transducer, the electrical pulse thus induced in it triggers a pulse generator whose output is taken back to the same marker transducer. The marker transducer now becomes an ultrasound transmitter producing a visible signal - mark that marks its position in the echographic image on the screen. The next step in the procedure is the actual controlled puncture. To do this one pushes out the needle and punctures the adjacent tissue. The establishment of the protrusion of the needle into the tissue is done with the said transponder method whereby the needle is ultrasonically marked. The depth of the puncture is done by ultrasound pulse ranging of the distance between the marker transducers on both the introducer catheter and the needled catheter. A separate electronic circuit measures the said distance by measuring the transit time of ultrasound pulses between the said two marker transducers. Thus this invention solves the problem of guidance and control of puncture procedures in the heart. This invention, therefore, comprises the following said devices: the ultrasonically marked introducer catheter through which an ultrasonically marked needled catheter can be moved and the transponder circuits for ultrasound echography guidance as well as the ultrasound pulse ranging circuit.
Background and prior art Implantation and positioning of cardiac catheters for therapy delivering is at present mostly facilitated by X-ray imaging methods. The disadvantages of the X- ray methods are the ionizing radiation hazard and poor imaging of soft tissues, e.g. papillary muscles, interventricular septum, cardiac valves etc. Ultrasonic imaging is well suited for soft tissues and presents no X-ray hazard, but has the disadvantage of imaging in one plane tomographically. Using ultrasonic imaging, the flexible leads can be imaged, but the tip or any other part of interest cannot be positively identified since the apparent tip in the image can just be the point at which the lead leaves or enters the scanning plane. Ultrasonography has therefore fairly rarely been used for cardiac catheters imaging. The use was limited to some sonographically suitable circumstances and to pregnancy where X-ray imaging is not recommended. In order to improve the localization of electrodes and catheter tips on the cardiac leads we developed ultrasonically marked catheters and leads. Various approaches to guiding intracardiac and Minimum Invasive Surgery (MIS) procedures have been proposed.
Attempts have been made to make a MIS device sensitive to ultrasound by using the needle as a solid ultrasound wave-guide as per US Pat no. 4,431,006 to Trimmer, Garduineer, Hadjikostis. This works only for solid, basically non-flexible devices.
A transducer mounted at the tip of a flexible MIS device for ultrasound Doppler measurements as per US Pat no. 4,771 ,788 to Millar can be used to intraluminally detect blood flow velocity. Similarly a device with an ultrasound ranging device in US Pat no. 5,893,848 to Negus, Linhares, Rudko and Woodruff might be used to determine the depth of lesions induced by MIS, similar to forward looking ultrasound echo-ranging transducer from US Pat no. 6,024,703 to Zanelli, Giba, Davis, Murphy-Chutorian as well as in US Pat no. 6,086,534 to Kesten. Other axial ranging systems include the annular piezoelectric transducer as per US Pat no. 6024703 to Zanelli, Giba, Davis and Murphy-Chutorian. In the US Pat no 6,206,831 and 6,508,765 to Suorsa, Swanson, Panescu, TenHoff and Whayne
ultrasound transducers are used both for ultrasonic ablation and for distance measurement. Performance of all these ranging devices for guidance strongly depends on individual interpretation of A-mode onscreen images.
Attempts have been made to combine ultrasound scanning imaging probes with MIS devices as per US Pat no 5,024,234 to Leary and McKenzie. A similar concept from the standpoint of guidance can be found in US Pat no. 5,409,000 to Imran. Very high frequency ultrasound scanning probes combined with laser therapy devices have been devised in US Pat no 5,109,859 to Jenkins. In US Pat no. 6,546,276 to Zanelli the distance and alignment with the heart wall is measured using a multitude of ultrasound transducer elements mounted at the perimeter near the tip of a MIS device. These devices are too expensive to be disposable and yield only side view. Therefore these devices can have a very narrow field of applications within the scope of the problem we are solving.
X-ray equipment may be used for the navigation in conjunction with a specific dispenser of radio opaque markers, as per US Pat no. 6,030,377 to Linhares, Negus, Rudko and Woodruff but our intention is to avoid ionizing radiation.
In US Pat no 6216027 and US Pat no. 6,490,474 to Willis, Brisken, Zeng and Hurd reference ultrasound transducers are positioned within the patient's heart and other marker transducers are than used to determine the position of the marker transducers by triangulation and thus guide certain in-heart procedures. A considerable number of devices must thus be indwelled in the heart, which makes it less practical a solution for our purposes.
Our solution to the problem is based on the application of the concept of ultrasound scanners in conjunction with ultrasonically marked catheters and MIS devices. Ultrasound scanners are presently available in almost all physicians' offices and in all hospitals.
Langberg (JACC Vol.12, No.1 , July 1988:218-23) teaches how to localize the catheter and its electrode within the heart by utilizing our invention described in our US Patents 4,697,595 and 4,706,681 , as clearly cited by him at the introduction and in the references though not citing these patent references. In our US Patent no.5,840,030, we show how to use directional ablation field with an indirect method of "energy visualization" within the echocardiographic image by knowing the directivity relation between the two fields: ultrasonic field and ablation field and how to monitor the electrode contact with the tissue. In US Patent No. 5,385,148 Lesh shows how to ultrasonically characterize the tissue. The localization function can be accomplished in two ways: either by using a transponder or by using a passive localization system. The transponder is triggered by signals from the marker transducer routed through the lead. Upon triggering, the transponder generates a characteristic series of electrical pulses, which are taken back to the same marker transducer, which, therefore, transmits a series of ultrasound pulses. These pulses appear at the echograph screen as a visible mark adjacent to the marked part of the lead irrespective of whether the lead itself is clearly discernible or not. The mark appears along the line-of-sight of the scanner as a white blinking pattern. The passive localization system comprises a time doubling circuit (TDC) which doubles the time elapsed between the transmission of an ultrasound pulse from the scanner probe and its reception by the marker transducer and then triggers a mark signal generator. This signal is taken to the signal bus of the ultrasonic scanner in the desired shape, polarity and time sequence. The system comprises medical grade isolation circuits for electrical shock safety according to the IEC 601-1 standard for CF class equipment. Accuracy of the localization depends on the physical dimensions and positioning of the marker transducer as well as on the beam width and sensitivity of the system. With the presently available piezoelectric transducers, the length of the marker transducer can be reduced to 1.5mm, yielding, with the present design a lengthwise positioning error of about 2mm. In cardiac catheter applications one normally needs only one mark shape, but in electrophysiology applications one must have multiple mark forms for
discerning the different electrodes. A passive system has a greater flexibility in this respect than the transponder. The passive system is scanner-specific in design. The ultrasonic marking system can help in avoiding a significant part of the use of X-rays in cardiac catheterization and lead implantation or electrophysiological studies. In addition it could help detection of the lead malfunctions. The radiation dose to the hands of the operator can easily reach 300 micro grays per application so that trying to avoid the use of X-rays when possible is justified. These and other aspects were pertinently described in our scientific papers B. Breyer, B. Ferek-Petric & I. Cikes. Properties of Ultrasonically Marked Leads. Pacing and Clinical Electrophysiology. Vol.12, (1989), p.1369., and B.Breyer & B. Ferek-Petric. Possibilities of Ultrasound Catheters. Int.Journ. of Cardiac Imaging, Vol.6., (1991), p. 277.
Disclosure of the invention It is the principal object of this invention to enable exact control over the direction and depth of therapeutic or diagnostic punctures within the heart or other structures in the body that are normally accessible only with catheters or similar devices. This puncture may serve to administer some medical agent into the punctured tissues. The said agent may be stem cells, a gene agent, a chemotherapy agent or any type of injectable drug. In a case when implantation is required at a well-defined depth, our invention serves to strictly control this depth. The advantage of the diagnostic aspect of such a puncture is again the strict control over the puncture depth. Another object of this invention is to guide and localize exact points of delivery of medical therapy that is performed by injection or instillation of some medical agent directly into human tissues in places within the body that are not visible or cannot be made visible by optical means but can be imaged by ultrasound echography. The puncture is done in two steps, namely, the first step is to bring the puncture set to the right place and in contact with the tissue to be punctured, and the second step is the actual puncture with administration of a medical agent or aspiration of a diagnostic sample.
The said puncture is done with a specific set of puncture catheters. It consists of a hollow introducer catheter and within it (inside) another catheter with a puncture needle at its distal end. The inside member can be a flexible puncture needle. The introducer catheter is used to maneuver the tip of the device to the point of interest. The internal puncture catheter or flexible needle is than pushed out to perform a therapeutic or diagnostic puncture. Both, the exact positioning and exact puncture need guidance and control to make it essentially safer and more exact compared to a blind procedure. Guidance by x-rays is not completely adequate due to radiation hazard and due to the fact that soft tissues are poorly imaged by this method. Ultrasound scanning presents no radiation hazard to the patient and the medical staff and has superior soft tissue imaging capability. The visualization of the said catheter end and puncture needle tip is essential for ultrasonic guidance of said procedures with the puncture catheter set. The method for positive ultrasonic localization of a point on an indwelled device, e.g. the said outer or the said inner needle catheter, consists of ultrasonic marking of the catheter and the use of a transponder to generate a visible mark on the ultrasound scanner screen. This means that the present method includes an imaging ultrasound scanner and the herewith-described set of ultrasonically marked puncture catheters. One or more miniature piezoelectric marker transducers are mounted at the tip of the outside (introducer) catheter and a separate transducer is mounted onto the puncture (needled) catheter. The marker transducer electrodes (fired-on silver or similar) are connected to the electrical conductors that connect it along the catheter to an outside electrical connector at the proximal end of the catheters. When the transducer on the catheter tip is in the scanning area, ultrasound pulses from the transducer of the echoscope energize it. Thus generated high frequency pulses are taken via built-in electrical conductors to the localization electronic circuit. The most straightforward electronic circuitry for the purpose of the localization is a transponder. The transponder localization system is a pulse train generator triggered by signal from the said marker transducer when the marked part of the catheter is within the ultrasonic scanning plane or area. When an
ultrasonic pulse reaches the marker transducer, the electrical pulse thus induced in it triggers a pulse generator whose output is taken back to the same marker transducer. The marker transducer now becomes an ultrasound transmitter producing a visible signal - mark that marks its position in the echographic image on the screen. The method does not depend on whether the scanning is done in two or in three dimensions. By this procedure the first task of bringing the puncture catheter into position is accomplished. The next step in the procedure is the actual controlled puncture. To do this one pushes out the needle and punctures the adjacent tissue. The fact that the puncture has been performed must be established and the puncture depth must be measured. The establishment of the protrusion of the needle into the tissue is done with the said transponder method whereby the needle is ultrasonically marked. The depth of the puncture is done by ultrasound pulse ranging of the distance between the marker transducers on both the introducer catheter and the needled catheter. A separate electronic circuit measures the said distance by measuring the transit time of ultrasound pulses between the said two marker transducers. Thus the puncture depth is closely controlled. Thus this invention solves the problem of guidance and control of puncture procedures in the heart. This invention, therefore, comprises the following said devices: the ultrasonically marked introducer catheter through which a ultrasonically marked needled catheter can be moved and the transponder circuits for ultrasound echography guidance as well as the ultrasound pulse ranging circuit.
Brief description of the drawings Referring to figure 1: The septum is punctured using a puncture catheter set that is introduced into the right heart ventricle. The introducer catheter 1 marked with the marker transducer 2 is positioned in the right heart. Through this introducer catheter, another catheter, the needle catheter 11 marked with the marker transducer 12 is introduced and the needle 13 is pushed forward and thus punctures a heart structure 10, in this case the interventricular septum.
Referring to figure 2: The hollow catheter 1 is marked with a transducer 2 that is connected to the proximal side of the catheter 1 with lengthwise conductors 3 and 4. Another, internal catheter 11 with a puncturing needle 13 at its tip is marked with a piezoelectric marker transducer 12. Lengthwise conductors 5 and 6 connect the marker transducer 12 to the proximal side of the catheter 11.
Referring to figure 3: The hollow catheter 1 is marked with a transducer 2 that is connected to the proximal side of the catheter 1 with lengthwise conductors 3 and 4. Another, internal catheter 111 with a puncturing needle 13 at its tip is marked with a piezoelectric marker transducer 12. Lengthwise conductors 105 and 106 connect the marker transducer 12 to the proximal side of the catheter 111.
Referring to figure 4: The ultrasound scanner 30 is used for imaging of the interior of the patient's body 33. The scanner probe 34 scans an 35 area within the patient's body. The said catheter 1 is inserted into the body and connected to the marking circuitry 37, e.g. transponders. The catheter set as described in figures 1. 2, 3 is marked with the marker transducers 2 and 12. When the said marker transducers 2 or 12 are within the imaged area 35 the marking circuitry 37 generates such electrical signals as to generate visible and recognizable marks on the screen of the ultrasound scanner 30.
Referring to figure 5: The marking circuitry is double if there are two marking transducers as illustrated in figures 1 and 2. As illustrated in figure 5, the circuitry consists of two transponders or equivalent circuits 42 and 44 and ranging parts 41 and 43. These are interconnected with appropriate switching circuitry 45 and to the catheter set 1 from figures 1 , 2, 3, 4 via switching and connection circuitry 47. A controlling circuit 46 is used to coordinate the operation of the separate parts.
Referring to figure 6: The marking circuitry can have a multiplexer switch 55 to operate as double if there are two marking transducers 2 and 12 as illustrated in figures 1 and 2. As illustrated in figure 6, the circuitry consists of one transponder 52 and ranging circuits 51 and 56. These are interconnected with appropriate
switching circuitry 55 and to the catheter set 1 from figures 1, 2, 3, 4 via switching and connection circuitry 57 and 58. A controlling circuit 55 is used to coordinate the operation of the separate parts.
Description of preferred embodiments As illustrated in figure 1 , the problem to be solved is guidance and control of puncture of some structure within the living heart. The guidance means bringing the device up to the desired structure in the body. The control means that the puncture procedure is controlled by close control of the depth of the puncture as measured from the surface of the structure. The puncture can be diagnostic or therapeutic. Therapeutic punctures include delivery of gene therapy, chemotherapy of delivery of any other medical agent. An outer guiding means in the form of a flexible catheter 1 containing another flexible puncture catheter or needle 11 is indwelled and positioned at a point of interest 10, in the illustrated case the interventricular septum. The practical problem is the control of this positioning. This is done using an ultrasound scanner with which one can, in real time, see both the soft tissue structures of the heart and the said catheters. However, due to the continuous movement and small dimensions of the said devices the exact position of the tip that contains the needle 13 is hard to know without the present technological invention. In order to solve this problem a marker transducer 2 is mounted onto the outer catheter 1 and another marker transducer 12 is mounted onto the internal device 11. This internal device 11 is axially movable within the outer catheter 1 and can be pushed such as to expose the puncture needle 13, thus puncturing the structure of interest 10. An external ultrasound echo scanner and a transponder are used in conjunction with the said catheter assembly. The said catheters are in more detail illustrated in figures 2 and 3. In the embodiment shown in figures 2A and 2B the outer catheter 1 is of the steerable kind so its distal part can be bent in at least one axis using outside controls. As seen in figure 2A, a piezoelectric transducer 2 is mounted adjacent to
the tip of catheter 1. This transducer, that can be a composite transducer made up of a multitude of transducers is connected the proximal part of the catheter by electrical conductors 3 and 4 and can deliver and accept electrical signals to and from electronic circuitry connected to it. Another catheter 11 of smaller diameter is positioned within the catheter 1 and can fully be retracted into it. It bears a puncture needle 13 or other device on its tip. The needle is shown as protruding from the outer catheter 1 , but during maneuvering within the body the needle can fully be retracted so that it does not penetrate anything until the ultimate target is reached. Once the target is reached the therapeutic or diagnostic puncture can be effected by pushing the inner catheter 11 out (figure 2B), thus exposing the needle 13 that penetrates the tissue in front of the device. At the same time a second marker transducer 12 is exposed and can deliver and accept electrical signals to and from electronic circuitry connected to it via internal electrical conductors 5 and 6 that lead to the proximal side of the said catheter 11 and can be connected to appropriate circuitry that we shall describe later. The needle 13 is a hollow needle that is used for therapeutic punctures to deliver medical agents via the hollow catheter 11 through the hollow needle 13 into the bodily structure 10 to be treated. In the embodiment illustrated in figures 3A and 3B the outer catheter 1 is of the steerable kind so its distal part can be bent in at least one axis using outside controls. As seen in figure 3A, a piezoelectric transducer 2 is mounted adjacent to the tip of catheter 1. This transducer, that can be a composite transducer made up of a multitude of transducers is connected the proximal part of the catheter by electrical conductors 3 and 4 and can deliver and accept electrical signals to and from electronic circuitry connected to it. Another catheter 111 of smaller diameter is positioned within the catheter 1 and can fully be retracted into it. It can be pushed out to the side from the catheter 1. It bears a puncture needle 13 or other device on its tip. The needle is shown as protruding from the outer catheter 1 , but during maneuvering within the body the needle can fully be retracted so that it does not penetrate anything until the ultimate target is reached. Once the target is reached the therapeutic or diagnostic puncture can be effected by pushing the inner catheter 111 out (figure 2B), thus exposing the needle 13 that penetrates the tissue at the side of the device. At the same time a second marker transducer 12 is exposed and can deliver and accept electrical signals to and from electronic
circuitry connected to it via internal electrical conductors 5 and 6 that lead to the proximal side of the said catheter 111 and can be connected to appropriate circuitry that we shall describe later. The needle 13 is a hollow needle that is used for therapeutic punctures to deliver medical agents via the hollow catheter 111 through the hollow needle 13 into the bodily structure 10 to be treated. This procedure can be used in cases when the structure to be treated is better accessed by leaning the steerable catheter 1 against it or when this structure is narrow, e.g. a blood vessel. The said puncture procedures are guided and controlled using outside ultrasound echo scanner means and a dedicated localization circuitry as illustrated in figure 4. The ultrasound scanner 30 images the area 35 within the human body 33. The said catheter assembly 1 which is the outer guiding means that is described with the help of figures 1, 2, 3 is indwelled in the body. Among other parts already described it bears two piezoelectric marker transducer assemblies 2 and 12 that are connected to electronic circuits 37 and 38 via conductors within the catheter assembly. When ultrasound pulses from the scanner probe 34 hit the piezoelectric marker transducers 2 and 12 electrical signals are generated and taken to the circuit 37 that is preferably a transponder. A transponder is a device that generates a characteristic electrical signal upon reception of a signal from a piezoelectric transducer and sends this characteristic electrical signal, called the signature, back to the transducer from which it was triggered. The electronic circuitry used in this invention is adapted to the two different tasks that need to be accomplished by the present device, namely the guidance of the device to its intended position and control of the puncture procedure. In accordance with the first aspect of this invention the catheter assembly 1 is guided to the desired position by the use of the outside ultrasound scanner 30 in conjunction with a transponder 37 or other equivalent positioning circuit. In accordance with the second aspect of this invention, the depth and success of the puncture is determined and controlled by measurement of the distance between the said marker transducers 2 and 12 using ultrasound pulse ranging circuitry 38. In more detail, there are various possibilities for embodiment of the outlined basic principle.
As illustrated in figure 5 it is possible to use two transponders 42 and 44 that are connected to the marker transducer 2 and 12 respectively. These are connected via the switch 45 during the guidance phase. Each of the said transponders generates its own electric and consequently a characteristic ultrasound pulse burst called the signature. These different signatures yield different marks on the screen of the scanner 30. Once the point of interest is reached and the catheter 1 leans against it, the second catheter 11 is pushed out so that the needle 13 penetrates the tissue, e.g. cardiac ventricular septum. The depth the needle penetrates is controlled by measurement of the distance between the marker transducers 2 and 12. For this purpose the two transducers are switched over to ranging circuits 41 and 43 via the switch 45 and under the control of the controlling circuitry 46 that can be manipulated by the operator. This ultrasound pulse ranging circuitry essentially measures ultrasound pulse transit time and is known in the art. The marker transducers can be switched 45 back and forth between the said two sets of electronic circuits at will. It is possible to use a single transponder as illustrated in figure 6. In this case a single transponder 52 is used and switched back and forth between marker transducers 2 and 12 using the switch 57. The controller 53 controls the rate of the switching between the two transducers. Once the point of interest is reached and the catheter 1 leans against it, the second catheter 11 is pushed out so that the needle 13 penetrates the tissue, e.g. cardiac ventricular septum. The depth the needle penetrates is controlled by measurement of the distance between the marker transducers 2 and 12. For this purpose the two transducers are switched over to ranging circuits 51 and 56 via the switches 55 and 58 respectively and under the control of the controlling circuitry 53 that can be manipulated by the operator. This ultrasound pulse ranging circuitry essentially measures ultrasound pulse transit time and is known in the art. The marker transducers can be switched back and forth between the said two sets of electronic circuits using switching circuits 55, 57, 58. The previously mentioned objects of guiding the active tip of the device for delivery of medical agent to the bodily structure of interest and subsequent control of the puncture procedure for the said delivery are thus achieved.